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Age-related Disturbances in DNA (hydroxy)methylation in APP/PS1 Mice.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Chouliaras, Leonidas  ORCID logo  https://orcid.org/0000-0002-3052-3879
Lardenoije, Roy 
Kenis, Gunter 
Mastroeni, Diego 
Hof, Patrick R 

Abstract

Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer's disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

Description

Keywords

APPswe/PS1ΔE9, Aging, Alzheimer’s Disease, DNA hy-droxymethylation, DNA methylation, Epigenetics

Journal Title

Transl Neurosci

Conference Name

Journal ISSN

2081-3856
2081-6936

Volume Title

9

Publisher

Walter de Gruyter GmbH